Multimodal molecular imaging reveals high target uptake and specificity of 111In and 68Ga labeled fibrin-binding probes for thrombus detection in rats

摘要

We recently showed the high target specificity and favorable imaging properties of ⁶⁴Cu and Al¹⁸F positron emission tomography (PET) probes for non-invasive imaging of thrombosis. Here, our aim was to evaluate new derivatives labeled with either with ⁶⁸Ga, ¹¹¹In, or ^99mTc as thrombus imaging agents for PET and single-photon emission computed tomography (SPECT). In this study, the feasibility and potential of these probes for thrombus imaging was assessed in detail in two animal models of arterial thrombosis. The specificity of the probes was further evaluated using a triple-isotope approach with multimodal SPECT/PET/CT imaging.MethodsRadiotracers were synthesized using a known fibrin-binding peptide conjugated to NODAGA, DOTA-MA, or a diethylenetriamine ligand (DETA-PA), followed by labeling with ⁶⁸Ga (FBP14, ⁶⁸Ga-NODAGA), ¹¹¹In (FBP15, ¹¹¹In-DOTA-MA) or ^99mTc (FBP16, ^99mTc(CO)3-DETA-PA), respectively. PET or SPECT imaging, biodistribution, pharmacokinetics and metabolic stability were evaluated in rat models of mural and occlusive carotid artery thrombosis. In vivo target specificity was evaluated by comparing the distribution of the SPECT and PET probes with preformed ¹²⁵I-labeled thrombi and with a non-binding control probe using SPECT/PET/CT imaging.